A temporal comparison of BOLD, ASL, and NIRS hemodynamic responses to motor stimuli in adult humans

Abstract

In this study, we have preformed simultaneous near-infrared spectroscopy (NIRS) along with BOLD (blood oxygen level dependent) and ASL (arterial spin labeling)-based fMRI during an event-related motor activity in human subjects in order to compare the temporal dynamics of the hemodynamic responses recorded in each method. These measurements have allowed us to examine the validity of the biophysical models underlying each modality and, as a result, gain greater insight into the hemodynamic responses to neuronal activation. Although prior studies have examined the relationships between these two methodologies through similar experiments, they have produced conflicting results in the literature for a variety of reasons. Here, by employing a short-duration, event-related motor task, we have been able to emphasize the subtle temporal differences between the hemodynamic parameters with a high contrast-to-noise ratio. As a result of this improved experimental design, we are able to report that the fMRI measured BOLD response is more correlated with the NIRS measure of deoxy-hemoglobin (R = 0.98; P < 10(-20)) than with oxy-hemoglobin (R = 0.71), or total hemoglobin (R = 0.53). This result was predicted from the theoretical grounds of the BOLD response and is in agreement with several previous works [Toronov, V.A.W., Choi, J.H., Wolf, M., Michalos, A., Gratton, E., Hueber, D., 2001. "Investigation of human brain hemodynamics by simultaneous near-infrared spectroscopy and functional magnetic resonance imaging." Med. Phys. 28 (4) 521-527.; MacIntosh, B.J., Klassen, L.M., Menon, R.S., 2003. "Transient hemodynamics during a breath hold challenge in a two part functional imaging study with simultaneous near-infrared spectroscopy in adult humans". NeuroImage 20 1246-1252.; Toronov, V.A.W., Walker, S., Gupta, R., Choi, J.H., Gratton, E., Hueber, D., Webb, A., 2003. "The roles of changes in deoxyhemoglobin concentration and regional cerebral blood volume in the fMRI BOLD signal" Neuroimage 19 (4) 1521-1531]. These data have also allowed us to examine more detailed measurement models of the fMRI signal and comment on the roles of the oxygen saturation and blood volume contributions to the BOLD response. In addition, we found high correlation between the NIRS measured total hemoglobin and ASL measured cerebral blood flow (R = 0.91; P < 10(-10)) and oxy-hemoglobin with flow (R = 0.83; P < 10(-05)) as predicted by the biophysical models. Finally, we note a significant amount of cross-modality, correlated, inter-subject variability in amplitude change and time-to-peak of the hemodynamic response. The observed co-variance in these parameters between subjects is in agreement with hemodynamic models and provides further support that fMRI and NIRS have similar vascular sensitivity.

Fig. 1

Probe design and placement for NIRS measurements. This probe consisted of 8 detector positions (most medial and lateral rows) and 4 source positions (middle row). The source detector separation was 2.9 cm. This probe was positioned approximately over the subject’s contra-lateral primary motor cortex as the subject lay in the MRI scanner. The probe also contains vitamin E rings placed on the caps of the optodes, which allowed registration of the optode array in the MR structural image (shown in Fig. 2).

Fig. 2

The NIRS probe placement was determined from vitamin E fiducial markers, which showed in the MPRAGE structural MR images. fMRI regions-of-interest were selected from significant (P < 0.01) pixels manually located under the probe. In all cases, this included all pixels within the primary motor area. Images (A and B) above show maximum intensity projections demonstrating the location of the probe on a sample subject. Image (C) shows the preparation for simultaneous acquisition of the fMRI and NIRS, demonstrating the positioned probe on a MRI subject.

Fig. 3

Here, we show a typical hemodynamic response for one subject as recorded by the NIRS instrument. Subplot (A) shows the region-of-interest averaged results obtained from averaging across all significant (P < 0.01) source detector pairs for all 6 runs. The error bars shown are the standard error across the same channels. Plot (B) shows the total array of source detector pairs that were recorded during the scan. Those that were used in the region-of-interest average are circled.

Fig. 4

Here we display the hemodynamic response functions for each of the five individual subjects used in study I. The maximum change of each parameter has been normalized to unity and the HbR response has been inverted for comparison. In each of the five subjects, the BOLD signal closely tracks the HbR measurement.

Fig. 5

Here, we display the five subject averaged hemodynamic response function for both the NIRS and BOLD responses. Curves were calculated from the average of the five normalized responses shown in Fig. 4. Again, the maximum change has been normalized to unity and the HbR response has been inverted. The error bars on plot (A) show the standard error of each time point from this average. Plot (B) is a zoomed scaling of the same data highlighting the response peaks. Like the individual results, the BOLD signal closely tracks the HbR measurement.

Fig. 6

These parametric plots show the linear correlation between HbO, HbT, and HbR (from left to right) and BOLD. The plots on top represent all individual data from the five subjects. The plots on the bottom show only the subject averaged response functions. The arrows (shown only on the averaged data) indicate the direction of time in the data. The linear correlation coefficients are presented in the bottom of each plot.

Fig. 7

Here we display the BOLD, ASL, and NIRS hemodynamic response functions for each of the five individual subjects used in study II. The maximum change of each parameter has been normalized to unity and the HbR response has been inverted for comparison.

Fig. 8

These parametric plots show the linear correlation between HbO, HbT, and HbR (from left to right) and ASL. Again, the images on top represent all individual data from the five subjects. The plots on the bottom show only the subject averaged response functions. The arrows (shown only on the averaged data) indicate the direction of time in the data. The linear correlation coefficients are presented in the bottom of each plot.

Fig. 9

Here, we present the group averaged response functions from simultaneous NIRS and ASL-fMRI scans (study II). As was also seen in the individual subject data, the ASL measured CBF clearly peaks around 2 s earlier then the BOLD response. The NIRS measured HbT/HbO and HbR responses closely agree with the fMRI responses of CBF and BOLD respectively. The figure on the right shows a zoomed view of the same response, highlighting the clear separation in time-to-peak between the HbO:HbT:ASL and HbR:BOLD responses.